This application is designed to investigate the function of specific T lymphocyte subsets in the process of recovery from experimental pulmonary viral infection and to ascertain the role of specific lymphokines, particularly interferon gamma (IFN gamma) in the process of virus clearance mediated by these T lymphocyte subsets. The experimental approach employs clonal populations of T lymphocytes directed to type A influenza virus and a model system of adoptive transfer of these characterized T lymphocyte clones into influenza infected syngenetic recipient mice. Immunization strategies designed to specifically stimulate selected T cell subsets in vivo will also be examined. The objectives of the proposed studies are (1) to characterize the T helper 2 (Th2) response to type A influenza in the mouse at the clonal level; (2) to define the role of specific lymphokines in the recovery process mediated by specific T lymphocyte populations; and (3) to assess the role of antigen form and mode of immunization on the induction of specific T lymphocyte subsets in vivo. The work will also employ neutralizing monoclonal antibodies to specific lymphokines and antisense oligodeoxynucleotides to examine the role of specific lymphokines in recovery mediated by T lymphocyte clones in vivo. This investigation should provide basic information on the role of different T lymphocyte subsets in antiviral immunity and should as well provide insight into the mechanism by which T lymphocytes orchestrate antiviral responses in vivo. These studies may also provide a rational framework for the use of specific T lymphocyte populations for adoptive immunotherapy in man.